We have already found and reported that several antitumor substances are obtained from meat portion of shellfish and exhibit wide antitumor spectra with little or no cytotoxicity (refer to Japanese Patent Publication No. 8088/82 and Japanese Patent KOKAI Nos. 41314/79 and 41315/79). To be concrete, the first substance we found is a water-soluble, thermally stable glycoprotein having a molecular weight range within the limits of 100,000 and 300,000 (Japanese Patent Publication No. 8088/82). Japanese Patent KOKAI No. 41314/79 describes four substances all of which are water-soluble glycoprotein substances having an average molecular weight of about 20,000 and an isoelectric point of pH 4.5 with somewhat different physical properties from one another and are extracted from meat portion of scallop from which the liver has been removed. Japanese Patent KOKAI No. 41315/79 provides a water-soluble glycoprotein substance having an average molecular weight of 10,000.about.30,000 which is obtained from meat portion of shellfish, particularly of scallop, wreath shell, tokobushi (Haliotis japonica) and pearl-oyster, from which the liver has been removed.
After that, we have further found that the liquid portion which comes from cooking of raw shellfish with a hot aqueous solvent or with the vapor of such solvent for taking up edible portions thereof and which is to be discarded as waste can also serve as raw material from which water-soluble, macromolecular glycoprotein substances similar to those already obtained from shellfish as above-mentioned are recovered and that these substances have a range of molecular weights within the limits of from 10,000 to 300,000 and possess a significant antitumor activity (refer to T. Sasaki et al, U.S. patent application Ser. No. 404,971, now U.S. Pat. No. 4,390,468).
Thus, the known antitumor substances derived from shellfish may be divided into two broad classes, namely water-soluble glycoproteins having a molecular weight range within the limits of 10,000 and 30,000, typically of around 20,000, and those having a molecular weight range within the limits of 100,000 and 300,000.
We have continued our investigations on antitumor substances derived from mollusc, particularly from shellfish, with the intention of obtaining novel antitumor substances which possess wide antitumor spectra with low cytotoxicities and which exhibit high antitumor activities particularly against solid tumors which are known to be difficult in clinical treatment thereof and discovered such phenomenon on a dry powder derived from the liquid portion to be discarded as waste which comes from the cooking of raw scallop in an aqueous solvent such as water or a saline solution or with vapor of such solvent as being inexplainable from the nature and properties of known antitumor substances of the same origin already reported. On the basis of this discovery, we have followed up our study thereon and successfully isolated a new antitumor substance of a relatively low molecular weight from the dry powder.
Among so-called chemotherapeutic agents, one of the most interesting classes is antitumor substances possessing immunostimulating or immunopotentiating activities. Since, however, known antitumor substances are of relatively high molecular weight, in general, there is a fear of anaphylaxis to occur due to antigen-antibody reaction resulting from the administration of such a high molecular weight substance. In contrast, the antitumor substance according to this invention is of relatively low molecular weight which thus seems to have little such a fear, so that it is expected and interested to be of high value as antitumor agent.